laser treatment options for onychomycosis - a review
DESCRIPTION
Presentation during European Academy of Dermatology and Venerology in the European Society of Laser Dermatology session.TRANSCRIPT
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Onychomycosis are laser and light sources effective?
Review of evidence
Wojciech Francuzik, Klaus Fritz, Anna Janecka
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no conflict of interests
DISCLOSURE:
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Questions
• Is there a need for laser treatment ?
• Is it effective ?
• Is it proven ?
• Which parameters ?
• Is it economically reasonable ?
Review of evidence
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• Is there a need for laser treatment ?
• Is it effective ?
• Is it proven ?
• Which parameters ?
• Is it economically reasonable ?
Questions
Review of evidence
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Toe Fungus Alternate Treatment Options
• Poor current treatment alternatives – Daily lacquer ---10% success rate
• Requires ~1 year of application to achieve 10% success rate • Low cost but low success
– Oral medication (Lamisil & Sporanox) -- 50% success rate after 6 – 9 month program • High liver stress • Cannot repeat drug therapy if it does not work • Single active agent is not always effective in all types of fungus • Interaction with medication • Contraindicarion in many immunologic and other diseases
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The need for new therapeutic options
• To minimalize side effects
• Confine only to affected area
• Treatment options for patients with liver disease and multimorbidity
• Inability to develop microbial resistance
• Lack of mutagenic and genotoxic effects
Why are lasers attractive?
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Questions
• Is there a need for laser treatment ?
• Is it effective ?
• Is it proven ?
• Which parameters ?
• Is it economically reasonable ?
Review of evidence
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Studies on laser treatment effectivness in onycomycosis
in vitro in vivo
Vural et al.
Manevitch et al.
Aguilar et al.
Bornstein et al.
Harris et al.
Manevitch et al.
Aguilar et al.
Kozarev et Vizintin
Hochmanet al.
Landsman et al.
Weiss
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The effects of laser irradiation on Trichophyton rubrum growth.
Vural, E., et al. (2008) Lasers in medical science, 23(4), 349–353.
IN VITRO STUDY
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Laser systems proven ineffective on T. rubrum growth inhibition
Laser system Wavelength (nm)
Fluence (J/cm2)
IPL (Lumenis, Vasculight) 695 - 1000 38, 45, 57
IPL (Lumenis, Vasculight) 795 - 1000 38, 45, 57
Pulsed dye laser (Candela, SleroPlus) 585 8, 11, 14
Erbium YAG laser (Sciton Model Contour) 2940 25
KTP laser (Laserscope, Aura) 532 2, 4, 6, 8
Vural, E., et al. (2008) Lasers in medical science, 23(4), 349–353.
Propably Thermal damage plays secondary role
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Q-switched Nd:YAG of 532 and 1064 nm wavelengths and 4 – 8 J/cm2 fluencies
Laser systems proven effective on T. rubrum growth inhibition
CONCLUSION:
Nanosecond pulses of irradiation
Vural, E., et al. (2008) Lasers in medical science, 23(4), 349–353.
Microcavitation Acoustic shock
Thermal shock
T. rubrum cell
Xanthomeganin (absorbs 532 nm)
Melanin (absorbs 1064 nm)
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The Direct Antifungal Effect of 800 nm Femtocecond Laser on T. rubrum
IN VITRO STUDY
Methods:
Strain identification
Culture samples To verify fungal infection
SEM NAIL EXAMINATION
2-4 weeks
CONTROL
Sabuard + cyclohexamide
SUBCULTURE
Manevitch, Z., et al. (2010) Photochemistry and photobiology, 86(2), 476
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Laser used in Manevich et al. study:
Ti:Sapphire, femtosecond infra-red laser (MIRA 900, Coherent Radiation, Santa Clara, CA)
800 nm, 200 fsec pulses, 76 MHz frequency
– 800 nm allows to effectively transverse the nail and
is effective at any level – Good therapeutic index due to difference in fluences
• 4.8 x 1022 photons /s*m2 was effective, • 17 x 1022 photons /s*m2 was destructive
IN VITRO STUDY
Manevitch, Z., et al. (2010) Photochemistry and photobiology, 86(2), 476
CONCLUSION:
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T. Rubrum colonies
Nd:YAG 1320 nm
4 J/cm2
vacuum or cooling
treatment
No Effect of vacuum and thermal shock on laser treatment of T. rubrum
IN VITRO STUDY
Aguilar et al. Proc. of SPIE Vol. 7548 754805-7
1. Laser irradiated samples showed reduced colony growth compared to untreated samples
2. Vacuum or cooling had little or no effect on previously irradiated samples
CONCLUSION:
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In vitro studies
Vural et al. Q-switched Nd:YAG laser 532 nm and 1064 nm wavelengths
Inhibition of fungal colony growth
Manevitch et al. Femtosecond infrared
titanium sapphire, 800 nm
Complete clearance of T.rubrum infected
nail clippings
Aguilar et al.
Q-switched Nd:YAG laser, 1320 nm by vacuum and
thermal shock
Inhibition of T. rubrum colony
growth
Bornstein et al. Diode, 870/930 nm 4074 – 4500 J/cm2
Complete clearance of T. rubrum and
C.albicans
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OCT-
In vivo studies and clinical controls
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Background - Nail Anatomy
• Fingernails grow ~ 3 mm / month
– Takes 6 months for nail to grow out
• Toenails grow ~ 1 mm / month
– Takes 12-18 months for nail to grow out
• Diseased nails tend to grow slower then normal
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Treatment of nail fungus
Type of nail fungus pattern: Subungual and or nail bed Therapy by thermolysis needs maximum temperature in
fungus layers (for effectivity) and Minimal temperature in
uninvolved tissue (increases saftey , reduces
pain)
Onycho-
gryphosis
Nerves
Laser
Capillaries
Courtesy PinPointe
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Temperature distribution example: CoolBreeze
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Laser used: 1. COOLTOUCH
• Nd:YAG Q switched laser
• 1064 or 1320 nm wl
• 6-350 microsec
• 4mm beam diameter
• Fluence 4 J/cm2
• 50 ms pulse envelope
IN VITRO STUDY
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Reaches Target Temperature • Move the hand piece over the nail in different directions until the
target temperature is reached • Real time temperature is displayed • System will deliver cryogen spray when the set target
temperature is reached • Adjust target temperature to achieve a comfortable treatment for
the patient
Number of Passes • Repeat until all the nails have been treated to the target
temperature 2 times Treatment Interval • Every 2 - 6 weeks for a total of 3 to 4 treatments,depends on
condition of the nail, clinical response to treatment and rate of nail growth
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CoolBreeze 1064nm Laser Treatment
Photos courtesy of Ritchie Steed, DPM
6 weeks Post - Treatment Pre - treatment
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Post Treatment, 7.5 months
CoolBreeze™ 1320nm Laser Treatment
Photos courtesy of Ritchie Steed, DPM
6 weeks Post - Treatment Pre - treatment
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• Diode Laser
• Low power
• Requires the use of toe clips
• Treats 4 toes simultaniously
• Protocol requires three 6 min
procedures
Noveon (Nomir Technologies) Laser
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Noveon (Nomir Technologies) Laser
Bornstein, E., et al. Photochemistry and photobiology, 85(6), 1364–74.
Study In vitro
Bornstein et al. In vivo
Landsman et al.
Laser system Noveon, diode, 870/930 nm Noveon, diode, 870/930 nm
Power output (W) 11,0 3,0
Energy fluence (J/cm2)
4500 Over 720 sec
204 + 424 Over 120 + 240 sec
Total energy used in protocol 7920 J 360 + 750 J
Outcome 100% Clearance 38% negative cultures
after 3 x 6 min Tx
Landsman, A. S., et al. (2012) JAPMA, 102(2), 169–171.
IN VIVO
STUDY
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Laser treatment for toenail fungus
with PinPointe FootLaser
IN VIVO
STUDY
Harris, DM, et al. (2009) Proceedings of SPIE, 7161, 71610M–71610M–7.
3 months follow-up
79% (11/14) had over 3 mm of clear
nail growth in 90 days
L R
14 patients
NO -Tx Tx
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Laser specifications
IN VIVO
STUDY
Harris, DM, et al. (2009) Proceedings of SPIE, 7161, 71610M–71610M–7.
Laser used: PinPointe FootLaser, Patholase, Nd:YAG pulse laser, 1064nm wl
Approved by FDA, CE Mark Sigle treatment required
CONCLUSION:
Small sample size, (N=14) There was no culture after treatment Effectiveness is measured by „clear” nail growth
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Unique Pulse Modulation
• The PinPointe FootLaser’s unique combination of wavelength and pulse structure for targeting the fungus
• Laser pulse ends before there is damage to surrounding tissue-or pain to the patient
• Other Nd:YAG lasers can be very painful due to non-specific pulse modulation
LASER PRESETS
P1 P2 P3
PULSE ENERGY
200 mJ 200 mJ 200 mJ
REPETITION RATE
20 Hz 30 Hz 30 Hz
LASER ON TIME PER BURST
½ second ½ second 1/3 second
LASER OFF TIME PER BURST
½ second 1/6 second
1/3 second
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95% of negative cultures after 3
months and 100% after 6 months.
Laser treatment for toenail fungus with Dualis (Fotona) Laser
During each treatment visit:
3 treatment visits 12 month folow-up
No sideffects
RESULTS:
IN VIVO
STUDY
Kozarev, J., & Vižintin, Z. (2010) J Laser Health Academy, 1(1), 1–8
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Fotona Dualis Laser Specifications
IN VIVO
STUDY
Kozarev, J., & Vižintin, Z. (2010) J Laser Health Academy, 1(1), 1–8
CONCLUSION:
Effective but… Study lacks control group, (N=72)
The 1064 nm Nd:YAG laser was used with: 35-45 J/cm2 of fluence 30-35 msec of pulse duration 4 mm of spot size 1 Hz of frequency
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• Same methodology and protocol
• Only 37.14% (N=35) negative cultures after 3 months
• Possible causes: – 30% of patients had Scytalidium diminatum infection
– 14,3% of patients had dimished peripheral circulation
– Subungual hyperkeratosis?
FAILURE TO REPRODUCE RESULTS
Wanitphakdeedecha R, The Efficacy and Safety of 1064 nm Nd:YAG Laser in the Treatment of Onychomycosis – Thai Experiences
www.Fotona.com
IN VIVO
STUDY
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=
• 2 or 3 treatments 223 J/cm2 fluence,
2mm spot size
• Results: – Negative cultures in 7/8
patients
• Conclusion: – Non comparable results
– Small sample size
0.65 milisecond Nd:YAG 1064 nm
Hochman, L. G. (2011) Journal of cosmetic and laser therapy , 13(1), 2–5
IN VIVO
STUDY
Laser: LightPod Neo, Aerolase
1 pass 2 pass ANTIFUNGAL CREAM
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Visible aiming beam (coaxial with invisible treatment beam)
Visible working distance beam
Invisible Temperature
sensor
GenesisPlus (Cutera) Laser Specifications
Two aiming beams + Temp Sensor
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GenesisPlus (Cutera) Laser Specifications
IN VIVO
STUDY
The 1064 nm Nd:YAG laser was used with: 16 J/cm2 fluence 0,3 msec of pulse duration 5 mm of spot size 2 Hz of frequency
Goal for effective treatment is to heat and hold tissue temperature at 43o- 46o as indicated by yellow LEDs Use 700-800 pulses / 5 toes,
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GenesisPlus (Cutera) Laser Specifications
IN VIVO
STUDY
Weiss D. 3 Month Clinical Results using Sub-millisecond 1064 nm Nd : YAG Laser for the Treatment of Onychomycosis.
CONCLUSION:
70% of improvment in nail condition Study lacks control group, (N=7) No cultures post Tx
The 1064 nm Nd:YAG laser was used with: 16 J/cm2 fluence 0,3 msec of pulse duration 5 mm of spot size 2 Hz of frequency
Results base on a subjective
score of a single examiner!!!
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U. Kimura et al. study
IN VIVO
STUDY
Kimura U, et al. J Drugs Dermatol. 2012 Apr;11(4):496-504
CONCLUSION:
Very similar design to previous study 51% of microscopicly negative samples
Study lacks control group, (N=13)
The 1064 nm Nd:YAG laser was used with: 14 J/cm2 fluence 0,3 msec of pulse duration 5 mm of spot size 5 Hz of frequency
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Questions
Review of evidence
• Is there a need for laser treatment ?
• Is it effective ?
• Is it proven ?
• Which parameters ?
• Is it economically reasonable ?
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Nail Anatomy and Types of Onychomycosis Need to be defined in order to find the best technology
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Light Absorption in Tissue makes a difference
1 µm
10 µm
100 µm
1 mm
10 mm
100 mm
1 m
10 m
100 m
0.1 0.5 1 2 3 0.4 0.3 0.2
1064 Nd:YAG
Water
Wavelength
Hemoglobin
Melanin
1320 nm Nd:YAG
1320 nm is absorbed uniformly in water and tissue with little effect from melanin or hemoglobin
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1 µm
10 µm
100 µm
1 mm
10 mm
100 mm
1 m
10 m
100 m
0.1 0.5 1 2 3 0.4 0.3 0.2
1064 nm Nd:YAG
Water
Wavelength
Hemoglobin
Melanin 1064 nm is not as
well absorbed in water and tissue
Melanin or hemoglobin are the dominate chromophores
Light Absorption in Tissue makes a difference
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Summary and discussion
• Studies proove positive effects • Are hard to compare • Small sample sizes • Most had no control group • Some were not reproducible • Remissions: no comment
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Questions
• Is there a need for laser treatment ?
• Is it effective ?
• Is it proven ?
• Which parameters ?
• Is it economically reasonable ?
Review of evidence
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Is it economically reasonable ?
• Not reimbursed
• If effective 30-100 €/session
• Cost of device should not exceed 4 sessions in 100 patients = < 20 000 €
• Better : use an existing laser and adapt similar parameters for addititional pay off
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What’s next
• Photodynamic phototherapy?
• A standardized reasearch protocol
• Chromophore related laser treatment
• More studies on laser can be expected to find best wavelenghth and protocol
• Studies OCT controlled?
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OCT (optical coherence tomography)
may be useful in effectivity studies
OCT
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The Nail in OCT
Papillary Dermis
Naiel
Matrix
Eponychium
Courtesy PD Dr Messmer , Munich, Germanyou
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OCT: nail fungus
Courtesy PD Dr Messmer , Munich, Germanyou
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Hematoma
Courtesy PD Dr Messmer , Munich, Germanyou
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Thank You for Your attention
WHERE POZNAN MEETS PRAGUE
Wojciech Francuzik, Klaus Fritz, Anna Janecka